Radiation Therapy Dose Escalation Failed to Improve Local Control for Intermediate-Risk Rhabdomyosarcoma on ARST1431: A Report From the Children's Oncology Group.

Abstract

To evaluate local failure (LF) rates for patients with intermediate-risk rhabdomyosarcoma treated on the Children's Oncology Group ARST1431 clinical trial, the first and largest international, phase 3 randomized study to use FOXO1 fusion status for risk stratification. To improve local control, radiation therapy (RT) dose was increased to 59.4 Gy for patients with tumors >5 cm and residual gross disease at the time of RT. For the 297 patients included, LF was defined as progression or relapse at the primary site. The rate of LF was calculated 3-years after enrollment. LF for group 3, FOXO1 fusion-positive patients (n = 58) compared with fusion-negative patients (n = 175) was 10.7% versus 21.5%, respectively (P = .08). The LF rate for patients with tumors >5 cm at diagnosis (n = 180; 24.4%) was higher than that of patients with tumors ≤5 cm at diagnosis (n = 117; 9.8%), P = .002. The risk of LF for patients who received proton (n = 99) versus photon RT (n = 126) was not different (16.1% vs 15.9%, P = .8). For the 75 patients with tumors >5 cm at diagnosis and gross disease at the time of RT, the boost to 59.4 Gy did not improve the 3-year LF rate compared with that of patients who did not receive the boost (29.7% vs 16.1%, P = .6). For patients with group 3/4 disease, those who underwent delayed primary excision (n = 72) had a lower LF rate compared with those who had RT alone (n = 151) (5.8% vs 19.7%, P < .01). On ARST1431, tumors >5 cm at diagnosis had poor local control despite dose escalation to 59.4 Gy. Proton and photon RT had equivalent local control. For select patients, delayed primary excision significantly improved local control.